ArticleACS applied nano materials2026
Single-Particle Analysis of Cargo-Dependent Deformation in Lipid Nanoparticles Using Resistive Pulse Sensing: Implications for Formulation Optimization and Quality Control of mRNA Nanomedicine.
Article in ACS applied nano materials, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Lipid nanoparticles (LNPs) are widely used for mRNA delivery and gene therapy, with their functional performance and therapeutic efficacy closely linked to nanoscale mechanical properties and formulation consistency. Nanopore-based technique offers a label-free platform to resolve LNP size, translocation dynamics, and confinement-induced deformation. Here, we investigate three LNP formulations with defined mRNA cargo loading: empty LNPs (eLNP), partially loaded LNPs containing an average of approximately 7 mRNA copies (LNP1), and fully loaded LNPs containing an average of approximately 32 mRNA copies (LNP2), using nanopipette-based resistive pulse sensing. By systematically tuning the nanopipette diameter, we demonstrate that geometric confinement critically governs sensitivity to cargo-dependent LNP deformation. Nanopipettes with 350 nm pores provide weaker confinement and limited discrimination between LNP subpopulations, whereas stronger confinement with 250 nm pores markedly enhances sensitivity to deformation. Under increased electric-field strength in the smaller nanopipettes, eLNPs exhibit pronounced reductions in relative current blockade (Δ
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